Wulfenioidins D–N, Structurally Diverse Diterpenoids with Anti-Zika Virus Activity Isolated from Orthosiphon wulfenioides

Abstract

Eleven diterpenoids, wulfenioidins D−N (1−11), classified into five distinct carbon skeletons with one unreported framework, and four modified abietane diterpenoids were isolated from the whole plant of Orthosiphon wulfenioides. The structures and absolute configurations were characterized by spectroscopic methods, singlecrystal X-ray diffraction, and electronic circular dichroism analyses. Compounds 3 and 5 exhibited activity against Zika virus (ZIKV) with EC 50 values of 8.07 and 8.50 μM, respectively, and showed no significant cytotoxicity toward Vero cells at 100 μM. Western blot and immunofluorescence experiments showed that compounds 3 and 5 interfered with the replication of the ZIKV by inhibiting the expression of the ZIKV envelope (E) protein.

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“…Orthosiphon wulfenioides is the source of a range of rearranged abietane diterpenoids including wulfenioidins D 12 and G 13 . 10 Wulfenioidin D 12 has a novel skeleton and its structure and absolute configuration were established by X-ray analysis. Four monoterpene–chalcone conjugates have been isolated from Conamomum rubidium .…”

Retrosynthesis of Wulfenioidins L with Potential Anti-Zika Virus Activity

“…In a study published this year, Tu et al isolated eleven wulfenioidins from Orthosiphon wulfenioides [1]. Among these compounds, five demonstrated anti-Zika virus (ZIKV) activity.…”

“…Among these compounds, five demonstrated anti-Zika virus (ZIKV) activity. They inhibit the entry of the virus into cells by suppressing the expression of the ZIKV envelope (E) protein [1,2]. Compared to ribavirin, a ZIKV treatment known for causing damage to red blood cells, wulfenioidins show potential for a new treatment approach with lower toxicity [3].…”

“…Among these compounds, wulfenioidin L (Figure 1) is less potent compared to wulfenioidins F and H, and even to ZIKV ribavirin [1]. However, when wulfenioidins F and H face pharmacokinetic challenges, wulfenioidin L emerges as the best alternative.…”